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PBL PY2 Fall > Venous Thromboembolism Therapeutics Lecture 2 > Flashcards

Venous Thromboembolism Therapeutics Lecture 2 Flashcards

1
Q

DOACs were first approved in Canada in what year?

A

2008

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2
Q

which DOAC was the first to be approved in Canada?

A

Dabigatran

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3
Q

DOACs have a _____ response with fixed dosing

A

predictable

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4
Q

is anticoagulant monitoring required for DOACs?

A

no

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5
Q

t/f DOACs have fewer drug and food interactions than warfarin

A

t

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6
Q

what is the brand name of dabigatran?

A

Pradaxa

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7
Q

which of the DOACs is a pro-drug?

A

dabigatran

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8
Q

how is dabigatran etexilate changed into the active drug?

A

by esterase-catalysed hydrolysis in plasma and in the liver

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9
Q

Dabigatran is a ____ (competitive vs non-competitive) reversible direct ___ inhibitor

A

competitive; thrombin

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10
Q

what are the 3 indications for dabigatran?

A
  1. prevention of VTE in patients who had THR or TKR surgery
  2. treatment for VTE and prevention of recurrent VTE
  3. prevention of stroke and systemic embolism in patients with a fib
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11
Q

what is the dosing of dabigatran for a VTE?

A

150mg po bid after 5-10 days of LMWH

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12
Q

what is the dosing of dabigatran for extended VTE treatment?

A

150mg po bid

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13
Q

what is the dosing of pradaxa for A fib?

A

110 or 150mg po bid (consider 110mg if age >80 or >75 with bleeding risk)

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14
Q

What dose of pradaxa is used for knee/hip surgery?

A

110mg po once, then 220mg po daily (rarely used)

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15
Q

what are key counselling points for Pradaxa (Dabigatran)

A

it contains acids to help in its absorption and this may cause dyspepsia, but you should not not antacids, but you can take with food and this often resolves. It must be stored in the blister

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16
Q

what is the antidote for pradaxa?

A

idarucizumab (Praxbind)

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17
Q

what is idarucizumab?

A

reversal agent specific to dabigatran; it is a monoclonal antibody

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18
Q

what is the dose of idarucizumab to reverse dabigatran?

A

2 x 2.5g IV doses at a max of 15 min apart

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19
Q

how long does it take for idarucizumab to reverse anticoagulant effect?

A

minutes

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20
Q

what is an ADR of idarucizumab?

A

potential thrombosis

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21
Q

use of idarucizumab is restricted to what situations?

A

life-threatening bleeding and emergency surgeries

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22
Q

what is Rivaroxaban?

A

a highly selective, direct, antithrombin independent factor Xa inhibitor with high oral bioavailability

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23
Q

how do selective Xa inhibitors like rivaroxaban work?

A

stop the amplified burst of thrombin generation, thereby diminishing thrombin-mediated activation of coagulation

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24
Q

what are the 3 typical indications for Rivaroxaban?

A
  1. prevention of VTE in pts who have had TKR or THR
  2. treatment of DVT, PE and prevention of recurrent DVT and PE
  3. prevention of stroke and systemic embolism in patients with A fib in whom anticoagulation is appropriate
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25
Q

what are 2 newer indiactions for Rivaroxaban?

A
  1. prevention of stroke, MI, and cardiovascular death, and for the prevention of acute limb ischemia and mortality in patients with CAD with or without peripheral artery disease
  2. prevention of atherothrombotic events in patients with symptomatic PAD
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26
Q

dosing of xarelto for VTE

A

15mg po BID for 21 days. then 20mg po daily

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27
Q

what is the dosing of xarelto in extended VTE treatment?

A

10-20mg po daily

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28
Q

what is the xarelto dose in a fib?

A

20mg po uid

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29
Q

what is the xarelto dose in A fib if CrCl <50mL/min?

A

15mg po uid

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30
Q

xarelto dose for hip/knee surgery

A

10mg po daily for 14-35 days

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31
Q

xarelto dose for prophylaxis in medical patients

A

10mg po UID

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32
Q

xarelto dose for peripheral artery disease and CAD

A

2.5mg po BID with ASA 81mg daily

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33
Q

what is a special administration consultation point for xarelto?

A

the 20mg & 15mg tablets need to be taken with food to increase absorption

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34
Q

can xarelto tablets be crushed?

A

yes

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35
Q

what can be done if you miss a dose of xarelto?

A

if taking 15mg BID, you can double up at second dose, but do not double up in other situations

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36
Q

what is the antidote for xarelto?

A

andexanet alpha

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37
Q

what is the new formulation of xarelto? In what patient population is it used in?

A

granules for dispersion; peds

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38
Q

t/f there is evidence that xarelto can reduce hospitalization time

A

true

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39
Q

what is the drug class of abixaban?

A

direct Xa inhibitor

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40
Q

what are the 3 indications for abixaban?

A
  1. prevention of VTE in adult patients who have undergone TKR or THR
  2. prevention of stroke and systemic embolism in patients with A fib
  3. treatment of VTE and prevention of recurrent DVT and PE
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41
Q

what is the name brand for apixaban?

A

eliquis

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42
Q

apixaban dosing for VTE treatment

A

10mg po BID for 7 days, then 5 mg po bid

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43
Q

what is dosage for extended treatment of VTE with apixaban?

A

2.5-5mg po bid

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44
Q

abixaban dosage for A fib

A

5mg po bid

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45
Q

what is the abixaban dosing for A fib if they have 2/3: age >80, weight <60kg, SCr >133`

A

2.5mg po bid

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46
Q

t/f there is a little evidence for the use of apixaban in end stage renal disease, and is sometimes used even in dialysis

A

t

47
Q

apixaban dosage for hip/knee prophylaxis

A

2.5mg po bid

48
Q

does apixaban need to be taken with food?

A

can be with or without

49
Q

can apixaban be crushed?

A

yes

50
Q

what can be done if patient misses a dose of apixaban?

A

can double up only if on 10mg po BID

51
Q

what is the antidote for apixaban?

A

andexanet alpha

52
Q

what are the Canadian and USA brand names for edoxaban?

A

lixiana and savaysa

53
Q

what drug class is edoxaban?

A

direct factor Xa inhibitor

54
Q

what are the 2 main indications for edoxaban?

A
  1. prevention of stroke & systemic embolic events in patients with A Fib
  2. treatment of VTE and the prevention of recurrent DVT and PE
55
Q

what indication of edoxaban’s “claim to fame”?

A

cancer associated thrombosis treatment

56
Q

edoxaban dosage for VTE

A

60mg po uid following 5-10 days of LMWH treatment

57
Q

what is the dosing of edoxaban for A fib?

A

60mg po uid

58
Q

for both VTE and A fib treatment with edoxaban, what is the dose adjustment if CrCl is 30-50ml/min, age over 80 or PGP interactions?

A

30mg po uid

59
Q

what is a benefit of edoxaban?

A

less prone to drug interactions

60
Q

what is the antidote for edoxaban?

A

andexanet alfa

61
Q

when on an anticoagulant, you may consider starting a ___ in some patients to reduce GI bleeding

A

PPI

62
Q

list some drugs that affect hemostasis and would interact with anticoagulants

A
  1. asprin and other antiplatelet agents
  2. SSRIs
  3. SNRIs
  4. NSAIDs when used chronically
  5. fibrinolytics
63
Q

what does ASH recommend if patients require administration of inhibitors or inducers of PGP or strong inhibitors or inducers of CYP enzymes?

A

alternative anticoagulants like VKA or LMWH (not DOACs)

64
Q

DOAC ____ is mediated by PGP

A

absorption

65
Q

CYP3A4 enzymes are involved in the metabolism of what class of DOAC?

A

Xa inhibitors (not dabigatran)

66
Q

give 3 examples of PGP inducers that would lower DOAC concentrations

A

carbamazepine, phenytoin, barbiturates

67
Q

give 3 examples of CYP3A4 inducers that would lower DOAC levels

A

carbamazepine, phenytoin, barbiturates

68
Q

andexanet alpha is the reversal agent for ____, but can be used for ___ as well

A

oral Xa inhibitors; LMWH and fondaparinux

69
Q

what is the MOA of andexanet alfa?

A

it is just recombinant factor Xa, so it replaces the Xa inhibited by Xa inhibitors

70
Q

how long does it take for andexanet alfa to reverse the effects of Xa inhibitors?

A

2 minutes

71
Q

what is an ADR of andexanet alfa?

A

thrombosis

72
Q

will PTT be higher or lower if the patient has HIT?

A

will be higher (bc there are fewer platelets to form a clot and it will take longer)

73
Q

if there is a minimal change in PTT for dabigatran or edoxaban therapy does it mean the therapy is not working?

A

no, these drugs do not have a major effect on this lab value

74
Q

which drugs give the most noticable increase in PTT?

A

UFH, argatroban and dabigatran (direct thrombin inhibitors)

75
Q

heparin treatment should be limited to ____days to reduce risk for HIT (if possible)

A

5

76
Q

you should avoid using heparin within ____days of previous heparin use

A

100

77
Q

UFH should be stopped ___hrs before surgery

A

4-6

78
Q

LMWH should be stopped ___hrs before surgery

A

24

79
Q

if patient has normal renal function and is scheduled for a low bleeding risk procedure, when should their dabigatran be stopped?

A

24 hrs before

80
Q

if a patient has normal renal function and is scheduled for a high bleeding risk procedure, when should their dabigatran be stopped?

A

48 hrs before

81
Q

if a patient has eGFR of 50-79 and is scheduled for a low bleeding risk procedure, when should you stop their dabigatran?

A

24-48 hrs beofre

82
Q

if a patient has eGFR of 50-79 and is scheduled for a high bleeding risk procedure, when should you stop their dabigatran?

A

48-72 hrs before

83
Q

if a patient has a eGFR of 30-49 and low bleeding risk procedure, when should you stop their dabigatran?

A

48-72 hrs before

84
Q

is a patient has a eGFR of 30-49 and scheduled for a high bleeding risk procedure, when should you stop their dabigatran?

A

96hrs before

85
Q

dabigatran should not be used if eGFR is below ___ml/min

A

30

86
Q

if a patient has eGFR of 30+ and is scheduled for a low bleeding risk procedure, when should you stop their apixaban, rivaroxaban, or edoxaban?

A

24 hrs before

87
Q

if a patient has a eGFR of 30+ and is scheduled for a high bleeding risk procedure, when should you stop their apixaban, rivaroxaban, or edoxaban?

A

48hrs before

88
Q

is a patient has a eGFR of 15-29 and is scheduled for. low bleeding risk procedure, when should you stop their apixaban, rivaroxaban, or edoxaban?

A

48hrs before

89
Q

if a patient has a eGFR of 15-29 and is scheduled for a high bleeding risk procedure, when should you stop their apixaban, rivaroxaban, or edoxaban?

A

72 hrs before

90
Q

warfarin should be stopped how long before surgery?

A

5 dyas before and INR needs to be checked the morning of surgery

91
Q

how long should fondaparinux be stopped before surgery?

A

36-42 hrs before

92
Q

if an IV bolus of heparin was given less than 1 hr ago, how much protamine is needed to reverse?

A

1mg/100u of heparin

93
Q

if an IV bolus of heparin was given 1-2 hours ago, how much protamine is required to reverse?

A

1mg/200u of heparin

94
Q

if a bolus of heparin was given more than 2 hrs ago, how much protamine is needed to reverse?

A

1mg/400U of heparin

95
Q

if an IV infusion of heparin was given within the past 2 hrs, what dose of protamine should be given to reverse?

A

1mg/100u heparin

96
Q

Px dose of rivaroxaban for TKRor THR?

A

10mg PO uid

97
Q

Px dose of apixaban of TKR or THR?

A

2.5mg UID

98
Q

px dose of dabigatran for TKR or THR?

A

220mg PO uid

99
Q

px dose of enoxaparin for TKR or THR?

A

30mg SC BID or 40mg UID

100
Q

px dose of dalteparin for TKR or THR

A

5000 U SQ uid

101
Q

Px dose of tinzaparin for THR or TKR?

A

4500 U or 75U/kg SQ uid

102
Q

Px dose of fondaparinux for THR or TKR?

A

2.5mg SQ uid

103
Q

duration of Px therapy for TKR or THR

A

14-35 days

104
Q

Px dose of enoxaparin for hip fracture surgery

A

30-40mg sq uid

105
Q

Px dose of dalteparin for hip fracture surgery

A

2500 or 5000U SQ uid

106
Q

Px dose of tinzaparin for hip fracture surgery

A

4500U sq uid

107
Q

Px dose of fondaparinux for hip fracture surgery

A

2.5mg SQ UID

108
Q

Px duration for hip fracture surgery

A

14-35 days

109
Q

what lab values should be checked before surgery?

A

INR, PT, PTT

110
Q

how long does it take for idarucizumab to reverse dabigatran?

A

less than 5 min

111
Q

dose of andexanet alfa to reverse DOACs, fondapariux, and enoxaparin

A

IV bolus 400/800mg; continuous infusion 4-8mg/min up to 120 min

112
Q

what lab test is used to test the efficacy of rivaroxaban?

A

anti Xa assay

113
Q

what are some advantages of DOACs over warafarin?

A
  1. does not require as much monitoring
  2. rivaroxaban may have lower risk of cerebral hemmorhage
  3. predictable response with fixed dosing
  4. fewer drug interactions
  5. can be switched more readily
114
Q

what are some advantages of warfarin over DOACs?

A
  1. cheaper

2. have been around longer, more research

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